Abstract P319: SARM1 NAD Hydrolase Deficiency Protects Hearts Against Diabetic Cardiomyopathy

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Christine Light ◽  
Chi Fung Lee
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Systolic Function ◽  
Whole Body ◽  
Male Mice ◽  
Progressive Decline ◽  
Nad Synthesis ◽  
Nad Depletion

NAD depletion is associated with the pathogenesis of diseases such as heart failure. Strategies to replenish cellular NAD levels by activating NAD synthesis pathways have shown promises to treat heart disease. However, how NAD consumption mechanisms lead to NAD depletion are less understood. SARM1 is a novel intracellular NAD hydrolase that degrades NAD and promotes axonal degeneration in neurons. We recently showed that NAD redox imbalance and depletion promote the progression of diabetic cardiomyopathy. Therefore, we hypothesized that SARM1 deficiency might protect hearts against diabetic cardiomyopathy. 16-week diabetic stress initiated by streptozotocin (STZ) injections was applied to wild-type C57BL/6 (WT) and whole-body SARM1-KO mice. Cardiac function was measured after 8-week or 16-week of diabetic stress, and cardiac tissue and plasma samples from these mice were harvested after 16 weeks of diabetes. SARM1 mRNA or protein levels were suppressed in SARM1-KO hearts. STZ induced similar hyperglycemia (~600 mg/dL) in both WT and SARM1-KO male mice after 16 weeks. Chronic diabetic stress led to progressive decline in systolic function (Baseline fractional shortening: 50%; 16-week diabetes: 35%; P<0.05; n=5) in WT male mice, which was ameliorated in SARM1-KO male mice (16-week diabetes: 48%; P<0.05; n=5). Progressive decline in diastolic function induced by chronic diabetes (Baseline WT E’/A’: 1.53; WT 16-week diabetes: 1.12; n=5) was also improved in diabetic SARM1-KO mice (KO E’/A’ ratio at 16-week diabetes: 1.5; P<0.05; n=5). Heart weights were similar in diabetic WT or diabetic SARM1-KO hearts. A similar study is on-going in a female cohort. Despite loss of SARM1 expression, no compensatory changes in expressions of other NAD hydrolases (i.e. Cd38 or Bst1) were observed in diabetic SARM1-KO hearts, while expression levels of genes related to NAD consumption and synthesis pathways were mostly unchanged except Qprt and Haao. Cardiac fibrosis was induced in diabetic WT hearts and were suppressed in diabetic SARM1-KO hearts after 16-week diabetic stress, but these changes were not observed in tissues harvested after 8-week diabetic stress. The results suggest fibrosis is a later event in the progression of diabetic cardiomyopathy. WT and SARM1-KO mice have also been challenged with high fat diet feeding (HFD) for 16 weeks, and increased fasting glucose levels and body weights were similarly observed in HFD-WT and HFD-SARM1-KO mice. Longitudinal cardiac function analyses are on-going. Our data thus far support the protective role of SARM1 deficiency in metabolic stress-induced cardiomyopathy, while pathogenic mechanisms of SARM1 in diabetic hearts remain to be determined.

Abstract P233: Diabetic Cardiomyopathy is Reversed by Increased Mitochondrial Bioenergetics Due to PGC-1α Activation by EET Treatment of Obese Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jian Cao ◽  
John A McClung ◽  
Shailendra P Singh ◽  
Lars Bellner ◽  
Maayan Waldman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Control Group ◽  
Protein Markers ◽  
Obesity And Diabetes

Introduction: Obesity and diabetes are associated with progressive cardiac fibrosis that, sequentially, results in diastolic dysfunction, reduced contractility, and ultimately heart failure. Contributing factors include hyperglycemia, insulin resistance, mitochondrial dysfunction, and a reduction in AMPK signaling. PGC-1α activates mitochondrial biogenesis and oxidative phosphorylation and is decreased in patients with diabetes mellitus (DM). We hypothesize that an epoxyeicosatrienoic acids (EETs) agonist (EET-A) will increase PGC-1α levels in a db mouse model of DM attenuate cardiomyopathy, and prevent heart failure. Methods: Db mice (4-wks), were allowed to acclimatize for 16-wks and were then divided into 3 treatment groups for an additional 16 wks: A) control, B) EET-A 1.5mg/100g BW 2 weeks and C) EET-A-Ln-PGC-1α shRNA. Ln-PGC-1α shRNA suppressed PGC-1α protein in heart tissue by 40-50%. Oxygen consumption (VO 2 ), and blood glucose was determined. Heart tissues were harvested to measure PGC-1α, HO-1, pAMPK, PGC-1α, echocardiographic fractional shortening, mitochondrial oxidative phosphorylation (OXPHOS) and mitofusion protein markers. Results: All mice developed heart failure by the end of 16 weeks and were characterized by a decrease in myocardial contractility, an increase in insulin resistance and blood pressure, decreased VO 2 , the appearance of mitochondria dysfunction and a decrease in AMPK and downstream PGC-1α signaling. Mice treated with EET-A demonstrated an increase in PGC-1α levels, improved mitochondrial function and oxidative phosphorylation (p<0.01 vs control), increased NO bioavailability (p<0.05 vs control), and normalization of glucose metabolism, insulin levels, VO 2 and LV systolic function (p<0.05 vs control). All of these findings were suppressed by PGC-1α inhibition which was accompanied by the onset of even more severe LV dysfunction than in the control group. Conclusion: Increased EET levels result in activation of PGC-1α-HO-1 which reverses diabetes induced insulin resistance, mitochondrial dysfunction, and cardiomyopathy. EET may have potential as a powerful agent for therapeutic application in the treatment of diabetic cardiomyopathy.

Abstract 315: Stromal Cell-derived Factor 1 Protects From Diabetic Cardiomyopathy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Xiaoqing Yan ◽  
Shudong Wang ◽  
Jing Chen ◽  
Jun Chen ◽  
Jun Zeng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Stromal Cell ◽  
Cardiac Tissue ◽  
Normal Diet ◽  
Citrate Buffer ◽  
Glucose Levels ◽  
Stromal Cell Derived Factor

We have demonstrated that stromal cell-derived factor 1(SDF-1) protects against palmitate-induced cardiac apoptosis, which is mediated by NOX-activated nitrosative damage and endoplasmic reticulum stress, via CXCR7, to activate AMPK/p38 MAPK-mediated IL-6 generation (Diabetes 62:2545-2558, 2013). Whether SDF-1 prevents diabetic cardiomyopathy has not been addressed. Here we evaluated the preventive effects of SDF-1 from diabetic cardiomyopathy in a high fat diet plus streptozotocin (HFD/STZ)-induced type 2 diabetic model in C57BL/6J mice. After 1 month on HFD, cardiac function was assayed by echocardiography, and then HFD-fed mice were injected with one low dose STZ (100mg/kg body weight, ip). Five days after STZ injection, mice with blood glucose levels ≥250 mg/dl were defined as diabetic. In parallel, the age-matched normal diet-fed mice injected with a same volume of citrate buffer (pH4.5) were used as control. After onset of diabetes, the mice were maintained on HFD or normal diet for another 4 months with or without SDF-1 treatment. Then cardiac function was assayed again, and the mice were sacrificed and cardiac tissue collected for cardiomyopathic index assay. We found that 1 month HFD feeding induced a significant insulin resistance without effect on cardiac function, but continued HFD feeding after STZ injection significantly impaired cardiac function, which were accompanied by increased insulin resistance and blood glucose, as well as blood insulin, triglyceride and cholesterol levels. Treatment with SDF-1 dose-dependently prevented diabetes-induced cardiac dysfunction but without significant effects on the above mentioned other pathophysiological parameters. These results indicate that SDF-1 possibly prevents diabetic cardiomyopathy via a direct cardiomyocyte action, which needs to be further defined in future study.

Mangiferin mitigates diabetic cardiomyopathy in streptozotocin-diabetic rats

2013 ◽  
Vol 91 (9) ◽  
pp. 759-763 ◽  
Author(s):  
Jun Hou ◽  
Dezhi Zheng ◽  
Guocheng Zhong ◽  
Yonghe Hu
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Matrix Metalloproteinase 2 ◽  
Severe Left Ventricular Dysfunction ◽  
Streptozotocin Diabetic Rats ◽  
Histopathologic Analysis ◽  
Myocardial Collagen

The purpose of this study was to investigate the cardioprotective effect of mangiferin on diabetic cardiomyopathy (DCM). The DCM model was induced by a high-fat diet and a low dose of streptozotocin. We evaluated the characteristics of DCM by serial echocardiography, electron microscopy, histopathologic analysis of cardiomyocyte fibrosis area, and Western blot analysis of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. Rats with DCM showed severe left ventricular dysfunction and cardiac fibrosis. Mangiferin mitigated DCM and prevented the accumulation of myocardial collagen. These anatomic findings were accompanied by significant improvements in cardiac function. Based on these results, we conclude that mangiferin has a therapeutic effect on DCM and improves cardiac function.

scholarly journals Neutrophil PAD4 negatively influences cardiac function and remodeling with increasing age

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Van Bruggen ◽  
J Van Wauwe ◽  
P Carai ◽  
L Frederix ◽  
L Vangilbergen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Essential Gene ◽  
Heart Function ◽  
Systolic Function ◽  
Natural Aging ◽  
Collagen Deposition ◽  
National Budget ◽  
Age Related

Abstract Background Aging can be viewed as a status of chronic inflammation, in which neutrophils have a lower threshold for activation. The enzyme peptidylarginine deiminase 4 (PAD4), which catalyzes the conversion of arginine to citrulline, will be activated in a certain population of neutrophils. When this conversion takes place on the histones, neutrophils can form neutrophil extracellular traps (NETs), which are both prothrombotic and proinflammatory. Mice lacking this enzyme systemically were previously reported to be protected from age-related fibrosis. Purpose We aimed to study the long-term effect of neutrophils on cardiac health during the process of natural aging. We hypothesized that neutrophil PAD4, and in consequence NETs, are involved in cardiac fibrosis development, which in turn will result in impaired cardiac function. Methods We generated a mouse model of impaired NET release capability via deletion of PAD4, a NET-essential gene, under the neutrophil-specific promoter (PAD4fl/flMRP8Cre+). In order to study heart failure (HF) development, these specific deletion mice and their littermate controls were aged for a period of two years (coinciding with approximately 70 years of age in the human population; the age at which HF is the number one cause of hospitalization), after which cardiac function and remodeling were evaluated by echocardiography and histology, respectively. A separate set of young mice (12 weeks) were evaluated in parallel. Results We performed a comprehensive echocardiography analysis including both structural and functional parameters. As for systolic function, we could see that in old wild type (WT) mice, ejection fraction (EF) significantly decreased as compared to EF in young and healthy (YH) mice (YH - 67±6%, WT - 53±10%; p&lt;0.0001) (Figure 1B). However, this decrease in systolic function was absent in the old PAD4fl/flMRP8Cre+ mice, with EF being comparable to the YH group (PAD4fl/flMRP8Cre+ - 67±7%; p=0.9169) (figure 1 A,B). As for diastolic function, again we could see a marked decrease in E/A ratio in the WT as compared to the YH population (YH- 1.50±0.23, WT – 1.21±0.17; p&lt;0.0001), while this functional deterioration was absent in aged PAD4fl/flMRP8Cre+ animals (PAD4fl/flMRP8Cre+ - 1.38±0.21; p=0.0837) (Figure 1 C,D). To link this decline in heart function to tissue remodeling, we quantified collagen deposition in the heart. We saw that natural aging resulted in an increase in cardiac collagen deposition in the WT population as compared to YH mice (YH – 0.86±0.63%, WT – 4.02±1.71%). This increased collagen deposition was absent in the neutrophil deletion mice (PAD4fl/flMRP8Cre+ - 1.7±0.76%). Additionally, when comparing WT to PAD4 deletion-mice, we saw that the increase in collagen deposition is significantly higher in the WT mice (p&lt;0.0001). Conclusion Our data confirms neutrophil PAD4 involvement in heart failure progression by promoting cardiac fibrosis, resulting in cardiac dysfunction. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek (FWO) - Vlaanderen

scholarly journals Role of Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Cardiac Tissue and Improvement of Cardiac Function: a Narrative Review

2020 ◽  
Vol 11 (1) ◽  
pp. 8446-8456
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Trichostatin A ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Point Of View

Recent efforts have made in order to novel therapeutic approaches to reduce the heavy cardiovascular burden. The use of cell therapy and applying stem cell-based therapies has received much attention; of particular interest are adipose-derived mesenchymal stem cells (ADSCs). The present review aimed to review the studies which examined and researched various aspects of ADSCs to improve cardiac function. A comprehensive review of all articles assessed and discussed the application of ADSCs in the improvement of cardiac tissue renewing and cardiomyocytes regeneration was planned and conducted by the two reviewers. The initial literature search revealed a total of 153 articles that, of those, 34 were considered eligible. From the perspective of heart tissue regeneration, the inductive role of ADSCs in sensing mechanical stimulation and produce collagen and elastin scaffolds, vascularizing cardiac tissue, and exosomes (vesicles derived from ADSCs) in ADSCs‐mediated myocardial protection has indicated. In the process of ADSCs differentiation to cardiomyocyte- like cells, the role of various targeted pathways have been identified that can be influenced by different elements such as TGF-beta1, phorbol myristate acetate, Angiotensin II, Rho-associated kinases, 5-Azaytidine, Sodium valproate, fibrin scaffold and trichostatin A have been highlighted. In the final, from a therapeutic point of view, the effectiveness of ADMSCs differentiation to cardiomyocytes as improving left ventricular functional state has been discussed. Summarizing the studies confirms a significant improvement in cardiac function following direct application of ADSCs or their transformation to cardiomyocytes by stimulating or inhibiting various cellular pathways leading reducing oxidative stress and inflammatory bed, reducing cardiomyocyte apoptosis, attenuating cardiac fibrosis, reducing the infiltration of immune cells and collagen deposition, and enhancing angiogenesis.

scholarly journals Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy

2010 ◽  
Vol 298 (3) ◽  
pp. H833-H843 ◽  
Author(s):  
M. Sulaiman ◽  
M. J. Matta ◽  
N. R. Sunderesan ◽  
M. P. Gupta ◽  
M. Periasamy ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Calcium Atpase ◽  
Dependent Manner ◽  
Protective Effects ◽  
Progressive Decline ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Dose Dependent

Reduced sarcoplasmic calcium ATPase (SERCA2a) expression has been shown to play a significant role in the cardiac dysfunction in diabetic cardiomyopathy. The mechanism of SERCA2a repression is, however, not known. This study was designed to examine the effect of resveratrol (RSV), a potent activator of SIRT1, on cardiac function and SERCA2a expression in chronic type 1 diabetes. Adult male mice were injected with streptozotocin (STZ) and fed with either a regular diet or a diet enriched with RSV. STZ administration produced progressive decline in cardiac function, associated with markedly reduced SERCA2a and SIRT1 protein levels and increased collagen deposition; RSV treatment to these mice had a tremendous beneficial effect both in terms of improving SERCA2a expression and on cardiac function. In cultured cardiomyocytes, RSV restored SERCA2 promoter activity, which was otherwise highly repressed in high-glucose media. Protective effects of RSV were found to be dependent on its ability to activate Silent information regulator (SIRT) 1. In cardiomyocytes, overexpression of SIRT1 was found sufficient to activate SERCA2 promoter in a dose-dependent manner. In contrast, pretreatment of cardiomyocytes with SIRT1 antagonist, splitomycin, blocked these beneficial effects of RSV. In addition, SIRT1 knockout (+/−) mice were also found to be more sensitive to STZ-induced decline in SERCA2a mRNA. The data demonstrate that, in chronic diabetes, 1) the enzymatic activity of cardiac SIRT1 is reduced, which contributes to reduced expression of SERCA2a and 2) through activation of SIRT1, RSV enhances expression of SERCA2a and improves cardiac function.

scholarly journals Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Peter Moritz Becher ◽  
Frauke Gotzhein ◽  
Karin Klingel ◽  
Felicitas Escher ◽  
Stefan Blankenberg ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Cardiac Fibroblasts ◽  
Viral Myocarditis ◽  
Coxsackievirus B3 ◽  
Long Term Effects ◽  
Cardiac Inflammation ◽  
Hemodynamic Function

Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function.Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling.Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

scholarly journals Sirtuin 3 Alleviates Diabetic Cardiomyopathy by Regulating TIGAR and Cardiomyocyte Metabolism

2021 ◽  
Author(s):  
Lanfang Li ◽  
Heng Zeng ◽  
Xiaochen He ◽  
Jian‐Xiong Chen
Keyword(s):  
Reactive Oxygen Species ◽  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Sirtuin 3 ◽  
Reactive Oxygen Species Formation ◽  
Species Formation

Background Impairment of glycolytic metabolism is suggested to contribute to diabetic cardiomyopathy. In this study, we explored the roles of SIRT3 (Sirtuin 3) on cardiomyocyte glucose metabolism and cardiac function. Methods and Results Exposure of H9c2 cardiomyocyte cell lines to high glucose (HG) (30 mmol/L) resulted in a gradual decrease in SIRT3 and 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase isoform 3 (PFKFB3) expression together with increases in p53 acetylation and TP53‐induced glycolysis and apoptosis regulator (TIGAR) expression. Glycolysis was significantly reduced in the cardiomyocyte exposed to HG. Transfection with adenovirus‐SIRT3 significantly increased PFKFB3 expression and reduced HG‐induced p53 acetylation and TIGAR expression. Overexpression of SIRT3 rescued impaired glycolysis and attenuated HG–induced reactive oxygen species formation and apoptosis. Knockdown of TIGAR in cardiomyocytes by using siRNA significantly increased PFKFB3 expression and glycolysis under hyperglycemic conditions. This was accompanied by a significant suppression of HG–induced reactive oxygen species formation and apoptosis. In vivo, overexpression of SIRT3 by an intravenous jugular vein injection of adenovirus‐SIRT3 resulted in a significant reduction of p53 acetylation and TIGAR expression together with upregulation of PFKFB3 expression in the heart of diabetic db/db mice at day 14. Overexpression of SIRT3 further reduced reactive oxygen species formation and blunted microvascular rarefaction in the diabetic db/db mouse hearts. Overexpression of SIRT3 significantly blunted cardiac fibrosis and hypertrophy and improved cardiac function at day 14. Conclusions Our study demonstrated that SIRT3 attenuated diabetic cardiomyopathy via regulating p53 acetylation and TIGAR expression. Therefore, SIRT3 may be a novel target for abnormal energy metabolism in diabetes mellitus.

miR-30a-5p inhibits the proliferation and collagen formation of cardiac fibroblasts in diabetic cardiomyopathy

2022 ◽  
pp. 1-9
Author(s):  
Xiao-xu Yang ◽  
Zhen-yu Zhao
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Cardiac Fibroblasts ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Collagen Formation ◽  
Gene Assay

Cardiac fibrosis is one of the major pathological characteristics of diabetic cardiomyopathy (DCM). MicroRNAs (miRNAs, miRs) have been identified as key regulators in the progression of cardiac fibrosis. This study aimed to investigate the role of miR-30a-5p in DCM and the underlying mechanism. The rat model of diabetes mellitus (DM) was established by streptozotocin injection, and the rat primary cardiac fibroblasts (CFs) were isolated from cardiac tissue and then treated with high glucose (HG). MTT assay was performed to assess the viability of CFs. Dual-luciferase reporter gene assay was conducted to verify the interaction between miR-30a-5p and Smad2. The expression of miR-30a-5p was downregulated in the myocardial tissues of DM rats and HG-stimulated CFs. Overexpression of miR-30a-5p reduced Smad2 levels and inhibited collagen formation in HG-stimulated CFs and DM rats, as well as decreased the proliferation of CFs induced by HG. Smad2 was a target of miR-30a-5p and its expression was inhibited by miR-30a-5p. Furthermore, the simultaneous overexpression of Smad2 and miR-30a-5p reversed the effect of miR-30a-5p overexpression alone in CFs. Our results indicated that miR-30a-5p reduced Smad2 expression and also induced a decrease in proliferation and collagen formation in DCM.

scholarly journals Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Yuanyuan Zhao ◽  
Xiaoxian Sun ◽  
Wenming Cao ◽  
Jie Ma ◽  
Li Sun ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Tube Formation ◽  
Human Umbilical Cord ◽  
Myocardial Cells ◽  
Ea.Hy926 Cells ◽  
And Migration ◽  
Cardiac Systolic Function

This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC-) derived exosomes (hucMSC-exosomes) have a protective effect on acute myocardial infarction (AMI). Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein) were intravenously administrated immediately following ligation of the left anterior descending (LAD) coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells). The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

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